title: Rickettsia Sca2 has evolved formin-like activity through a different molecular mechanism.
abstract: Sca2 (surface cell antigen 2) is the only bacterial protein known to promote both actin filament nucleation and profilin-dependent elongation, mimicking eukaryotic formins to assemble actin comet tails for Rickettsia motility. We show that Sca2's functional mimicry of formins is achieved through a unique mechanism. Unlike formins, Sca2 is monomeric, but has N- and C-terminal repeat domains (NRD and CRD) that interact with each other for processive barbed-end elongation. The crystal structure of NRD reveals a previously undescribed fold, consisting of helix-loop-helix repeats arranged into an overall crescent shape. CRD is predicted to share this fold and might form together with NRD, a doughnut-shaped formin-like structure. In between NRD and CRD, proline-rich sequences mediate the incorporation of profilin-actin for elongation, and WASP-homology 2 (WH2) domains recruit actin monomers for nucleation. Sca2's α-helical fold is unusual among Gram-negative autotransporters, which overwhelmingly fold as β-solenoids. Rickettsia has therefore "rediscovered" formin-like actin nucleation and elongation.
authors.affiliation: Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Yadaiah
authors.initials: Y
authors.lastname: Madasu
authors.forename: Cristian
authors.initials: C
authors.lastname: Suarez
authors.forename: David J
authors.initials: DJ
authors.lastname: Kast
authors.forename: David R
authors.initials: DR
authors.lastname: Kovar
authors.forename: Roberto
authors.initials: R
authors.lastname: Dominguez
mesh_terms: D000199:Actins / Q000378:metabolism*; D000942:Antigens, Bacterial / Q000737:chemistry / Q000378:metabolism*; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D002151:Calorimetry; D002942:Circular Dichroism; D003460:Crystallization; D019143:Evolution, Molecular; D005326:Fetal Proteins / Q000378:metabolism; D000080865:Formins; D008840:Microfilament Proteins / Q000737:chemistry / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D008958:Models, Molecular; D009687:Nuclear Proteins / Q000378:metabolism; D051304:Profilins / Q000378:metabolism; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D012281:Rickettsia / Q000235:genetics*; D020079:Terminal Repeat Sequences / Q000235:genetics
chemical_list: D000199:Actins; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D005326:Fetal Proteins; D000080865:Formins; D008840:Microfilament Proteins; D009687:Nuclear Proteins; D051304:Profilins
keywords: passenger domain; spotted fever; translocator domain